Impaired Axonal Transport in Motor Neurons Correlates with Clinical Prion Disease

Prion diseases are fatal neurodegenerative disorders causing motor dysfunctions, dementia and neuropathological changes such as spongiosis, astroglyosis and neuronal loss. The chain of events leading to the clinical disease and the role of distinct brain areas are still poorly understood. The role of nervous system integrity and axonal properties in prion pathology are still elusive. There is no evidence of both the functional axonal impairments in vivo and their connection with prion disease. We studied the functional axonal impairments in motor neurons at the onset of clinical prion disease using the combination of tracing as a functional assay for axonal transport with immunohistochemistry experiments. Well-established and novel confocal and ultramicroscopy techniques were used to image and quantify labeled neurons. Despite profound differences in the incubation times, 30% to 45% of neurons in the red nucleus of different mouse lines showed axonal transport impairments at the disease onset bilaterally after intracerebral prion inoculation and unilaterally—after inoculation into the right sciatic nerve. Up to 94% of motor cortex neurons also demonstrated transport defects upon analysis by alternative imaging methods. Our data connect axonal transport impairments with disease symptoms for different prion strains and inoculation routes and establish further insight on the development of prion pathology in vivo. The alterations in localization of the proteins involved in the retrograde axonal transport allow us to propose a mechanism of transport disruption, which involves Rab7-mediated cargo attachment to the dynein-dynactin pathway. These findings suggest novel targets for therapeutic and diagnostic approaches in the early stages of prion disease

The influence of prenatal environmental conditions on the weight of newborn domestic pigs

The weight of newborn piglets in domestic pigs depends on the maternal environment. Using an original algorithm based on the comparison of the coefficients of correlation between the half-nests (the same average genotype and the same conditions of the embryonic environment) and the twin sockets (the same genotype, different conditions of the embryonic environment), it was possible to estimate the relative contribution of the various components to the weight of the newborn in the domestic pigs. Our investigation found that the relative contribution of environmental conditions during prenatal development into newborn weight variation is equal to 0.4717, the contribution of genotypic component is 0.4032; the contribution of interaction between environmental conditions and ambivalence of the “genotype–phenotype” relationships is 0.0846, indeterminacy of phenotypic realization of the littermate’s genotypes is 0.0405. Maternal resource plays the main role amongst factors forming the environmental conditions of prenatal development. The gene pool will remain unchanged in any number of generations, despite a change in the population parameters of the trait. In principle, it can be assumed that when a population reaches a certain level, when the mean value of the trait and the gene pool are optimal (the selection pressure vectors are mutually balanced), selection becomes less effective in transforming the average phenotype than changing environmental conditions. Obviously, therefore, livestock maintenance and feeding are paid as much attention as breeding, and breeds of farmed animals are zoned

Articulation and Sharing of Distributed Design Project and Process Knowledge

The paper reports on the work in the case study of the AC-TIVE project on the use of the combination of knowledge process learning, articulation and sharing technologies for increasing the performance and decreasing the ramp-up efforts in engineering design projects. This knowledge is mined from distributed heterogeneous datasets, fused, and further used for visualizing design project plan information in a way that suggests optimized project plans and fosters collaboration on these knowledge structures in development teams. Software demonstrator architecture, implementation and validation are presented. Validation results indicate that the solution is effective in providing expert assistance to design project managers in performing their typical planning tasks

The Small-x Behaviour of the Singlet Polarized Structure Function g_2 in the Double Logarithmic Approximation

The small-x behavior of the singlet contributions to the polarized structure function g_2(x,Q^2) is calculated in the double-logarithmic approximation of perturbative QCD. The dominant contribution is due to the gluons which, in contrast to the unpolarized case, mix with the fermions also in the small-x domain. We find a power-like growth in 1/x in the odd-signature parts of the amplitude with the same power as in the singlet function g_1(x,Q^2) at x<< 1.Comment: 20 pages, latex, 3 ps figure

QCD explanation of oscillating hadron and jet multiplicity moments

Ratios of multiplicity moments, H_q (cumulant over factorial moments K_q/F_q), have been observed to show an oscillatory behaviour with respect to order, q. Recent studies of e^+e^- annihilations at LEP have shown, moreover, that the amplitude and oscillation length vary strongly with the jet resolution parameter y_{cut}. We study the predictions of the perturbative QCD parton cascade assuming low non-perturbative cut-off (Q_0\sim \Lambda_{QCD}\sim few 100 MeV) and derive the expectations as a function of the cms energy and jet resolution from threshold to very high energies. We consider numerical solutions of the evolution equations of gluodynamics in Double Logarithmic and Modified Leading Logarithmic Approximations (DLA,MLLA), as well as results from a parton MC with readjusted parameters. The main characteristics are obtained in MLLA, while a more numerically accurate description is obtained by the MC model. A unified description of correlations between hadrons and correlations between jets emerges, in particular for the transition region of small y_{cut}.Comment: 31 pages, 14 figure

СОВРЕМЕННАЯ МЕТОДИКА ОРГАНИЗАЦИИ ПРОЦЕССА РАЗРАБОТКИ ПРОГРАММ

.В статье рассматривается методика организации процесса разработки программного обеспечения на основе непрерывной интеграции, которая объединяет в единое целое множество техник, облегчающих разработку и сопровождение программ в промышленных масштабах.

N=4 SUSY Yang--Mills: three loops made simple(r)

We construct universal parton evolution equation that produces space- and time-like anomalous dimensions for the maximally super-symmetric N=4 Yang--Mills field theory model, and find that its kernel satisfies the Gribov--Lipatov reciprocity relation in three loops. Given a simple structure of the evolution kernel, this should help to generate the major part of multi-loop contributions to QCD anomalous dimensions, due to classical soft gluon radiation effects.Comment: 19 pages, 1 figur

Polymorphic loci of coat color in mini-pigs

The present work is phenomenological and purely descriptive. It shows polymorphism of colors in a breeding group of mini-pig in the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences (ICG SB RAS) and makes some assumptions about the nature of this genetic diversity. In the ICG SB RAS mini-pig herd, wild-type coloration (agouti), black-spots, black and white color are present. All these options have variants, including previously undescribed, with genetically determined differences. In addition, the ICG SB RAS mini-pigs have variants inherent only to heterozygous individuals and archaic gray color described only in primitive domestic pig. Comparison of the observed color phenotypes in the breeding with literature data showed that EDNRB, KIT, KITLG and the MC1R are polymorphic loci, while ASIP, OCA2 and TYRP1 are monomorphic loci. Thus, the loci that control the most common coat colors in domestic pigs are polymorphic, while those controlling rare or relatively rare colors and monomorphic. The research allowed us to put forward some assumptions concerning the genetic determination of the phenotypic characteristics of color seen in the study group selection. Among these assumptions is one about the genetic control of juvenile colors in domestic pigs. Observations made in the ICG SB RAS mini-pig breeding group allowed us to examine and describe the features of age-related changes of an embodiment of black-motley suit, when newborn piglets originally have black-and-motley fur color on the brick-red background and at an age of one year, a gray roan background formed by a mixture of white and black hairs. In addition, it was shown that with the help of technical means black spots can also be detected on a black background

Juvenile coat colours in mini-pigs at ICG

This article continues a previous study colors in minipigs at ICG. It also has a phenomenological character, but it consideres juvenile colour, which is an integral element of the ontogenetic formation of the suit, wild type agouti pigs of the species Sus scrofa L. However, in ICG mini pigs, in addition to individuals with the suit of the wild type, juvenile colour is a feature of pigs with the black spotted suit. It should be noted that data about a similar phenomenon in pigs with black spotted colour were not found in the literature. We proposed that a unique juvenile colour of black spotted mini-pigs ICG is a consequence of increased synthesis of pigments of hair, the intensity of which obviously exceeds the performance by the wild boar and domestic pigs. Newborn piglets of mini pigs ICG of the colour of the wild type typically have too little or too much yellow (orange, brown) pigment, which makes the figure of juvenile livery blurry – low contrast, or the lack of it, with the result that they are gray or gray-blue color with dark gray longitudinal stripes. The pattern of juvenile livery piglets of mini pigs ICG is disrupted. As a rule, instead of a longitudinal stripe, a mesh pattern livery is observed. Therefore, the agouti like colour observed in mini-pigs ICG should rather be called more properly pseudowild type. It was suggested that the specially planned crosses were able to “reveal” the genetic load of mutations in the complex of alleles involved in the formation of the suit of the wild type and accumulated in the population, not exposed to stabilizing selection on this archaic for domestic pigs’ colour. The accumulation of this genetic cargo at the mini-pigs was made possible by gipostatic suit wild type relative to epistatic colour standard for modern commercial plant breeds